Long Term Objective: To understand how the immune system of Drosophila melanogaster protects the fly from bacterial disease. Background: The blood of normal Drosophila contains no factors that kill bacteria, but the blood of flies inoculated with bacteria contains a newly synthesized set of polypeptides, the Antibacterial immune Response polypeptides (ARs), some of which (AntiBacterial polypeptides, ABs) kill bacteria. The overall problem is to determine how the fly recognizes the invading bacteria; how regulatory mechanisms result in the appearance of the immune polypeptides; and how the antibacterial proteins eliminate the bacterial invasion. Specific Aims: 1) To determine the molecular organization of Drosophila's antibacterial immune response genes; 2) To understand the mechanisms of induction of the immune response using a genetic approach. Methodology: Immune response genes will be cloned, and their structure analyzed. Mutations will be induced in immune response genes to identify their functions. Mutations that block the induction of immunity will be sought and their cellular and molecular phenotypes investigated to understand mechanisms that induce immunity. Potential Significance: 1) Progress in understanding basic molecular mechanisms regulating tissue-specific and environmentally induced gene expression. 2) Development of novel methodologies for controlling populations of insect vectors of human disease by blocking insect immunity.